Multidisciplinary approach to head and neck cancer

1. Multidisciplinary approach to head and neck cancer Kamil Konopka

2. Head and neck cancer (H&N)

3. What is head & neck cancer? • Squamous cell carcinoma (90%) • Mucoepidermoid carcinoma • Adenoid cystic carcinoma • Adenocarcinoma (lower esophagus) • Small-cell carcinoma • Esthesioneuroblastoma (olfactory neuroblastoma) • Lymphomas (Hodgkin & non-Hodgkin) • Sarcomas • Melanoma • Thyroid and parathyroid cancers • Metastases

4. What is head & neck cancer? Majority of H&N cancers are of squamus cell origin (90%) and therefore most of clinical guidelines based on EBM apply only to squamus cell cancer. Special subtypes (sarcomas, melanomas, metastases) treatment guidelines apply both to H&N region and origin site.

5. Epidemiology • How can an average patient with H&N cancer be described?

6. Epidemiology • Account for about 3% of all cancers • M/F ratio 3:1 • Avarge age : 50 to 70 y/o. • Frequency by site: • 44% oral cavity • 31% larynx • 25% pharynx

7. Etiology • Tabbaco and alcohol (>75%) : effect is synergistic • UV light exposure (cancer of lips) • Diet : poor diet, especially deficient in vit.A, C, chronic iron deficiency • Genetic susceptibility: germline mutations in p53 • Other enviromental agents: formaldehyde,wood dust (adenocarcinoma of the ethmoids, nasal cavity, paranasal sinuses), radiation exposure (salivary gland tumors)

8. Etiology • HPV(mainly oropharyngeal cancer, less often laryngeal and oral cavity cancer) • HSV-1, HSV-2 (oral cavity) • EBV (nasopharynx, some salivary gland tumors)

9. Field cancerization theory • Diffuse epithelial injury throughout the head and neck, lungs and esophagus that results from chronic exposure to carcinogens. • Lifetime risk of metachronus H&N cancer is 20-40%. • Local recurences are far more often than distant metastases.

10. Anatomy • Complexanatomy. • Drainagepatternsissystematic and predictable.

11. Summary • 3% of all cancers. • 90% of squamus cell carcinoma • Male 50-70, tabacco and alcohol abuse. • HPV infeciton • Field cancerization • Complex anatomy

12. Multidisciplinary team • Head and neck surgery • Radiation oncology • Medical oncology • Plastic and reconstructive surgery • Specialized nursing care • Dentistry/prosthodontics • Physical medicine and rehabilitation • Spech and swallowing therapy • Clinical social work • Nutrition support • Pathology (including cytopathology) • Diagnostic radiology • Adjunctive services: • Neurosurgery • Ophtalmology • Psychiatry • Addiction services • Audiology • Palliative care

13. Initial assessment • Physical examination and history • Head and neck endoscopy (biopsy) • Head and neck CT-scan (or MRI, USG) • Chest X-ray, thoracic CT-scan, abdominal USG/CT • PET/CT – if high risk of distant metastases

14. Signs and symptoms Alterations of deglutition, phonation, hearing,respiration. • dysphagia, • odynophagia, • globus sensation, • hoarseness, • a change in the ability to form words, • epistaxis, • epiphora, • otalgia, • hemoptysis, • stuffiness of the ears, • trismus

15. Signs and symptoms • ORAL CAVITY: swelling or ulcer that fails to heal, ipsilateral otalgia, leukoplakia and erythroplakia • OROPHARYNX:silent area (symptoms often delayed), dysphagia, odynophagia, otalgia, neck mass • HYPOPHARYNX: silent area, dysphagia, odynophagia, otalgia, neck mass • LARYNX:persistent hoarsness, pain, otalgia, dyspnea, stridor • NASOPHARYNX: bloody nasal discharge, obstructed nostril, unilateral conductive deafness (eustachian obstruction), neurologic problems (atypical facial pain, diplopia, hoarsness, Horner’s syndrome) resulting from cranial nerve involvement, asymptomatic neck mass

16. Signs and symptoms • NOSE AND SINUSES: bloody nasal discharge, nasal obstruction, facial pain,facial swelling, diplopia (direct orbital extension) • PAROTID AND SUBMANDIBULAR GLANDS: local swelling +/- pain, hemifacial paralysis owing to facial nerve involvement • A METASTATIC CERVICAL NODE: may be part of the clinical presentation of any of the above-mentioned tumours

17. Signs and symptoms • Red flags • Any symptom that lasted for more than 2 weeks • Any asymptomatic neck mass

18. Diagnostic imaging • X-ray • CT • MRI • PET-CT

19. Biopsy • Punch or cup forceps biopsy.  • FNA • Open biopsy

20. Pathology • Staging • Histologicgrade

21. Grade • G1 : >75% keratinization • G2 : 25-50% keratinization • G3 : <25% keratinization Not a consistentpredictor of clinicalbehavior. Markers of agresivebehaviour: • Perineuralspread • Lymphaticinvasion • Extracapsularextension

22. Staging • T score based on clinical/pathological characteristics of primary tumor • Different for every site • N/M score – similar for all sites

23. Staging • High impact on survival rates • Stage I >80% • Stage III/IV <40% Involvement of single lymph nodes decrease survival rate by 50%.

24. Principles of treatment • GOALS OF TREATMENT: a)Eradication of cancer b)Maintenance of adequate physiologic function of: -special senses (vision, hearing, balance, taste, smell) -mastication-deglutition (mandible, teeth, tongue, saliva, palate, pharynx, larynx) -respiration (larynx, trachea) -speech (larynx, tongue) c)acceptable cosmesis requires necessary but sufficient surgery, reconstructive surgical and prothesis rehabilitation MULTIDISCIPLINARY APPROACH HIGHLY RECOMMENDED

25. Treatmentalgorithm (oversimplified) Cancer Neoadjuvatn CTH Neoadjuvatn CTH Surgery Radical C/RTH Adjuvant RTH Adjuvant CRTH Salvagesurgery Followup

26. Principles of treatment: • EARLY STAGE DISEASE I, II (T1,T2,N0,M0) SINGLE MODALITY TREATMENT : SURGERY OR RADIOTHERAPY (brachytherapy) results achieved are equivalent

27. Principles of treatment • Decision on which modality should be choose is based onmainly on localization of tumor • Surgery : oral cavity • Radiotherapy : oropharynx, larynx, nasopharynx

28. Principles of treatment: ADVANTAGES OF SURGERY : -complete pathological staging of disease -quick local clearance of disease -avoidiance of toxicity of radiotherapy, including the risk of radiotherapy induced second malignancies ADVANTAGES OF RADIOTHERAPY: -avoidance of operative mortality in patients with significant comorbidities -organ conservation is more likely including preservation of the voice and swallowing -possibility of treatment of multiple synchronous primaries

29. Principles of treatment: • LATE STAGE DISEASE III and IV, RESECTABLE Combinedtreatment: SURGERY with adjuvant C/RTH or CHEMORADIOTHERAPY

30. Principles of treatment: COMBINED SURGERY + RADIOTHERAPY: 1. SURGERY + postsurgical RADIOTHERAPY -T3 – T4 primary tumour ->= N2 disease -perineural or vascular invasion -poorly differentiated tumor -short margins 2. SURGERY + postsurgical CHEMORADIOTHERAPY - positive surgical margins (cancer cells in surgical margin) - extracapsular extension

31. Principles of treatment: • LOCALLY ADVANCED UNRESECTABLE DISEASE –STAGE III, IV (M0) RADIOTHERAPY + CONCURRENT CHEMOTHERAPY -cisplatin most widely studied -modest survival advantage over RTH alone -increased toxicity especially mucositis

32. Treatmentalgorithm (oversimplified) Cancer Neoadjuvatn CTH Neoadjuvatn CTH Surgery Radical C/RTH Adjuvant RTH Adjuvant CRTH Salvagesurgery Followup

33. Principles of treatment: • CHEMOTHERAPY IN H&N TUMOURS: a)palliative treatment for metastatic or recurrent disease b)neoadjuvant chemotherapy c)concurrent with RTH in locally advanced H&N tumours: -improvement in locoregional control of the tumour d)Adjuvantchemotherapy (rarely) Impact on survial – 8%

34. Neoadjuvant chemotherapy • Performend before surgery or RTH in locally advanced disease. -reduction in distant metastases -shrinkage of tumour -organ preservation PF (cisplatin + 5FU) TPF (cisplatin + 5FU + paclitaxel) Recentstudies : negative

35. Biologic agent • Way to overcometoxicity of clasiccytotoxicdrugs (i.e. cisplatin) • Most widelystudied cetuximab (anty-EGFR antibody) • Used in conjunction with radiotherapy • Similaroutcomes to cisplatin, but much lowermorbidity • Less evidencethancisplatin.

36. Nivolumab

37. H&N cancer – recurrent and metastatic disease • Goal of treatment – curative/palliative • Combinedchemotherapy (2 cytotoxics) – platin-based (cisplatin, carboplatin) • Most frequentlyusedchemotherapyregimen: cisplatin + 5-fluorouracil • Addition of cetuximab to cispl/5FU chemotherapyimprovessurvival • For patients in worsegeneralstate: monotherapy (metothrexat) • Responserate 30% and survival of 6-12 months

38. Optimal way

39. HPV in H&N • Emerging data areclearlyindicatingthat in a subset with positive Human PapillomaVirus (HPV) the prognosismay be betterthan for the ordinarypatient with HNSCC • Thereare data underwaywhichindicatethatHPV infectionis the most prognosticfactorwhichoutnumbersboth Tumor and Nodal status, but thisevidenceyetneeds to be betterinvestigated

40. HPV-associated head and neck cancer: a virus-related cancerepidemic. Lancet Oncol 2010; 11: 781–89

41. TAX 324 trial:induction chemotherapy TPF vs PF  chemo-radiotherapy

42. Example • 58-year-old male patient with history of alcohol and tabacco abuse • Enlarged, palpable lymph nodes on posterior border of SCM muscle. • Palpable, ulcerated tumor in anterior 2/3 of tongue • Problems with swallowing, pain • Weight loss of 10 kg in last 4 months

44. Staging • CT scan of H&N : primary tumor : 3 cm • Single ipsilateral lymph nodes 2 cm. • Chest X-ray, USG : negative. • FNA : squamous cell carcinoma G2 • PS 0 • No serious comorbidites

47. Pretreatment : • Locoregional H&N squamous cell carcinoma • T2N1M0G2 • PS 0

49. Pathological report • pT3N2aG2 • Positive margins • 4 lymph nodes removed (1/4) • No additional risk factors

50. What now? • Second surgery (total glossectomy) • Radiochemiotherapy • Radiotherapy • Observation • ???